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Phase 2 Study of Modified FOLFOX versus Modified FOLFIRI in Patients with Locally Advanced or Metastatic Biliary Tract Cancer Refractory to First-Line Chemotherapy

August 2020, Vol 1, No 1

In patients with locally advanced or metastatic biliary tract cancer, treatment with second-line chemotherapy is challenging after disease progression from first-line gemcitabine plus cisplatin, although treatment with modified FOLFOX (mFOLFOX) has been proven to be superior to active symptom control in the ABC-06 trial.1 Irinotecan (Camptosar) is an active drug used in the treatment of various gastrointestinal cancers.

A phase 2 study, led by Jin Won Kim, MD, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea, evaluated whether mFOLFIRI was superior to mFOLFOX in the second-line treatment of patients with biliary tract cancer.2 The results of this study were presented at the 2020 ASCO annual meeting.

Patients who were diagnosed with biliary tract cancer and had disease progression after receiving gemcitabine plus cisplatin were randomized 1:1 to mFOLFOX or to mFOLFIRI. The randomization was stratified by tumor location (intrahepatic vs extrahepatic vs gallbladder vs ampulla of Vater) and Eastern Cooperative Oncology Group (ECOG) performance status (0-2). The primary end point was the overall survival (OS) rate at 6 months.

A total of 120 patients were enrolled in this study and 114 patients received treatment, including 56 patients who received mFOLFOX and 58 patients who received mFOLFIRI. The patients’ median age was 63 years. Most (89.5%) patients had ECOG status of 0 or 1. Tumor location was intrahepatic in 47 (41.2%) patients, extrahepatic in 27 (23.7%) patients, gallbladder in 35 (30.7%) patients, and ampulla of Vater in 5 (4.4%) patients.

At the median follow-up duration of 25.8 months, the 6-month OS rate was 54.2% in those who received mFOLFOX and 43.6% in the mFOLFIRI group. Of 101 evaluable patients (mFOLFOX, N = 51; mFOLFIRI, N = 50), the objective response rate was 5.9% with mFOLFOX and 66.7% with mFOLFIRI, and the disease control rate was 4% with mFOLFOX and 64.4% with mFOLFIRI.

The median progression-free survival was 2.8 months with mFOLFOX and 2.1 months with mFOLFIRI (P = .887). The median OS was 6.3 months with mFOLFOX and 5.7 months with mFOLFIRI (P = .472).

The most common grade 3 or 4 adverse events were neutropenia (25.0%) and aspartate transaminase or alanine transaminase elevation (16.1%) in the mFOLFOX group, and neutropenia (25.9%) and anemia (17.2%) in the mFOLFIRI group. Peripheral neuropathy (37.5%) and thrombocytopenia (37.5%) occurred more frequently in the mFOLFOX group, and vomiting (19.0%) and cholangitis (10.3%) occurred more frequently with mFOLFIRI. No chemotherapy-related deaths were reported.

The investigators concluded that the mFOLFIRI regimen was tolerable but not superior to mFOLFOX as second-line therapy for biliary tract cancer.


  1. Lamarca A, Palmer DH, Singh Wasan H, et al. ABC-06: a randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clin Oncol. 2019;37(15_suppl):Abstract 4003.
  2. Kim JW, Suh KJ, Kim J-W, et al. A randomized phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy. J Clin Oncol. 2020;38(15_suppl): Abstract 4603.

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